El trabajo

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

El recurso contencioso ante las Audiencias territoriales : contra los acuerdos de las Diputaciones provinciales anulando o declarando la validez de la elección de diputados provinciales

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-201

Delayed administration of VEGF rescues spinal motor neurons from death with a short effective time frame in excitotoxic experimental models in vivo

VEGF (vascular endothelial growth factor) prevents neuronal death in different models of ALS (amyotrophic lateral sclerosis), but few studies have addressed the efficacy of VEGF to protect motor neurons after the onset of symptoms, a critical point when considering VEGF as a potential therapeutic target for ALS. We studied the capability of VEGF to protect motor neurons after an excitotoxic challenge in two models of spinal neurodegeneration in rats induced by AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) administered either chronically with osmotic minipumps or acutely by microdialysis. VEGF was administered through osmotic minipumps in the chronic model or injected intracerebroventricularly in the acute model, and its effects were assessed by immunohistochemical and histological analyses and motor performance tests. In the chronic model, VEGF stopped the progression of the paralysis and protected motor neurons when administered after AMPA before the onset of the motor symptoms, whereas no protection was observed when administered after the onset. VEGF was also protective in the acute model, but with a short time window, since the protection was effective when administered 1 h but not 2 h after AMPA. Our results indicate that while VEGF has an indubitable neuroprotective effect, its therapeutic potential for halting or delaying the progression of motor neuron loss in ALS would likely have a short effective time frame

On the geometry of four qubit invariants

The geometry of four-qubit entanglement is investigated. We replace some of the polynomial invariants for four-qubits introduced recently by new ones of direct geometrical meaning. It is shown that these invariants describe four points, six lines and four planes in complex projective space ${\bf CP}^3$. For the generic entanglement class of stochastic local operations and classical communication they take a very simple form related to the elementary symmetric polynomials in four complex variables. Moreover, their magnitudes are entanglement monotones that fit nicely into the geometric set of $n$-qubit ones related to Grassmannians of $l$-planes found recently. We also show that in terms of these invariants the hyperdeterminant of order 24 in the four-qubit amplitudes takes a more instructive form than the previously published expressions available in the literature. Finally in order to understand two, three and four-qubit entanglement in geometric terms we propose a unified setting based on ${\bf CP}^3$ furnished with a fixed quadric.Comment: 19 page

Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production

With an increasing demand for efficacious, safe, and affordable vaccines for human and animal use, process intensification in cell culture-based viral vaccine production demands advanced process strategies to overcome the limitations of conventional batch cultivations. However, the use of fed-batch, perfusion, or continuous modes to drive processes at high cell density (HCD) and overextended operating times has so far been little explored in large-scale viral vaccine manufacturing. Also, possible reductions in cell-specific virus yields for HCD cultivations have been reported frequently. Taking into account that vaccine production is one of the most heavily regulated industries in the pharmaceutical sector with tough margins to meet, it is understandable that process intensification is being considered by both academia and industry as a next step toward more efficient viral vaccine production processes only recently. Compared to conventional batch processes, fed-batch and perfusion strategies could result in ten to a hundred times higher product yields. Both cultivation strategies can be implemented to achieve cell concentrations exceeding 10(7) cells/mL or even 10(8) cells/mL, while keeping low levels of metabolites that potentially inhibit cell growth and virus replication. The trend towards HCD processes is supported by development of GMP-compliant cultivation platforms, i.e., acoustic settlers, hollow fiber bioreactors, and hollow fiber-based perfusion systems including tangential flow filtration (TFF) or alternating tangential flow (ATF) technologies. In this review, these process modes are discussed in detail and compared with conventional batch processes based on productivity indicators such as space-time yield, cell concentration, and product titers. In addition, options for the production of viral vaccines in continuous multi-stage bioreactors such as two- and three-stage systems are addressed. While such systems have shown similar virus titers compared to batch cultivations, keeping high yields for extended production times is still a challenge. Overall, we demonstrate that process intensification of cell culture-based viral vaccine production can be realized by the consequent application of fed-batch, perfusion, and continuous systems with a significant increase in productivity. The potential for even further improvements is high, considering recent developments in establishment of new (designer) cell lines, better characterization of host cell metabolism, advances in media design, and the use of mathematical models as a tool for process optimization and control

S-matrix poles and the second virial coefficient

For cutoff potentials, a condition which is not a limitation for the calculation of physical systems, the S-matrix is meromorphic. We can express it in terms of its poles, and then calculate the quantum mechanical second virial coefficient of a neutral gas. Here, we take another look at this approach, and discuss the feasibility, attraction and problems of the method. Among concerns are the rate of convergence of the 'pole' expansion and the physical significance of the 'higher' poles.Comment: 20 pages, 8 tables, submitted to J. Mol. Phy

Experimental models for the study of neurodegeneration in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown cause, characterized by the selective and progressive death of both upper and lower motoneurons, leading to a progressive paralysis. Experimental animal models of the disease may provide knowledge of the pathophysiological mechanisms and allow the design and testing of therapeutic strategies, provided that they mimic as close as possible the symptoms and temporal progression of the human disease. The principal hypotheses proposed to explain the mechanisms of motoneuron degeneration have been studied mostly in models in vitro, such as primary cultures of fetal motoneurons, organotypic cultures of spinal cord sections from postnatal rodents and the motoneuron-like hybridoma cell line NSC-34. However, these models are flawed in the sense that they do not allow a direct correlation between motoneuron death and its physical consequences like paralysis. In vivo, the most widely used model is the transgenic mouse that bears a human mutant superoxide dismutase 1, the only known cause of ALS. The major disadvantage of this model is that it represents about 2%–3% of human ALS. In addition, there is a growing concern on the accuracy of these transgenic models and the extrapolations of the findings made in these animals to the clinics. Models of spontaneous motoneuron disease, like the wobbler and pmn mice, have been used aiming to understand the basic cellular mechanisms of motoneuron diseases, but these abnormalities are probably different from those occurring in ALS. Therefore, the design and testing of in vivo models of sporadic ALS, which accounts for >90% of the disease, is necessary. The main models of this type are based on the excitotoxic death of spinal motoneurons and might be useful even when there is no definitive demonstration that excitotoxicity is a cause of human ALS. Despite their difficulties, these models offer the best possibility to establish valid correlations between cellular alterations and motor behavior, although improvements are still necessary in order to produce a reliable and integrative model that accurately reproduces the cellular mechanisms of motoneuron degeneration in ALS

Second virial coefficient in one dimension, as a function of asymptotic quantities

A result from Dodd and Gibbs[1] for the second virial coefficient of particles in 1 dimension, subject to delta-function interactions, has been obtained by direct integration of the wave functions. It is shown that this result can be obtained from a phase shift formalism, if one includes the contribution of oscillating terms. The result is important in work to follow, for the third virial coefficient, for which a similar formalism is being developed. We examine a number of fine points in the quantum mechanical formalisms.Comment: 7 pages, no figures, submitted to Molecular Physic

Communication of Spin Directions with Product States and Finite Measurements

Total spin eigenstates can be used to intrinsically encode a direction, which can later be decoded by means of a quantum measurement. We study the optimal strategy that can be adopted if, as is likely in practical applications, only product states of $N$-spins are available. We obtain the asymptotic behaviour of the average fidelity which provides a proof that the optimal states must be entangled. We also give a prescription for constructing finite measurements for general encoding eigenstates.Comment: 4 pages, minor changes, version to appear in PR